Figures & data
Table 1. List of receptors which are found on different liver cells.
Table 2. Main patterns of liver injury during hepatotoxicity.
Table 3. Plants having hepatotoxicity.
Table 4. Drugs having hepatotoxicity.
Table 5. Industrial toxins causing hepatotoxicity.
Table 6. List of some medicinal preparations, which are approved by the IMPCPS (Indian Medicinal Practitioner’s Co-operative pharmacy and Stores), used for the treatment of various chronic liver disorders.
Table 7. List of some medicinal important plants found in India which are having hepatoprotective properties.
Table 8. Clinical significance of nanotechnological approaches which are having hepatoprotective properties.
Yang W, Zhang X, Liu Y. (2014). Asialoglycoprotein receptor-targeted radiopharmaceuticals for measurement of liver function. Curr Med Chem 21:4–23 Liu G, Bi Y, Wang R, et al. (2014). Targeting S1P1 receptor protects against murine immunological hepatic injury through myeloid-derived suppressor cells. J Immunol 192:3068–79 McDonald CJ, Wallace DF, Ostini L, Subramaniam VN. (2014). Parenteral vs. oral iron: influence on hepcidin signaling pathways through analysis of Hfe/Tfr2-null mice. Am J Physiol Gastrointest Liver Physiol 306:G132–9 Martinez LO, Jacquet S, Esteve J-P, et al. (2003). Ectopic β-chain of ATP synthase is an apolipoprotein AI receptor in hepatic HDL endocytosis. Nature 421:75–9 Goldstein JL, Brown MS. (2009). The LDL receptor. Arterioscl Thromb Vasc Biol 29:431–8 Jiang S, Gavrikova TA, Messina JL. (2014). Regulation of hepatic insulin receptor activity following injury. Am J Physiol Gastrointest Liver Physiol 306:G886–92 Li B, Yu M, Pan X, et al. (2014). Artesunate reduces serum lipopolysaccharide in cecal ligation/puncture mice via enhanced LPS internalization by macrophages through increased mRNA expression of scavenger receptors. Int J Mol Sci 15:1143–61 Ramirez-Garcia A, Arteta B, Abad-Diaz-De-Cerio A, et al. (2013). Candida albicans increases tumor cell adhesion to endothelial cells in vitro: intraspecific differences and importance of the mannose receptor. PLoS One 8:e53584 Storch K-F, Lipan O, Leykin I, et al. (2002). Extensive and divergent circadian gene expression in liver and heart. Nature 417:78–83 Rost MS, Sumanas S. (2014). Hyaluronic acid receptor stabilin-2 regulates Erk phosphorylation and arterial-venous differentiation in zebrafish. PLoS One 9:e88614 Friedman SL. (2008). Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 88:125–72 Kallis YN, Scotton CJ, Mackinnon AC, et al. (2014). Proteinase activated receptor 1 mediated fibrosis in a mouse model of liver injury: a role for bone marrow derived macrophages. PLoS One 9:e86241 Moss D, Powell LW, Halliday JW, et al. (1992). Functional roles of the ferritin receptors of human liver, hepatoma, lymphoid and erythroid cells. J Inorg Biochem 47:219–27 Strickland DK, Au DT, Cunfer P, Muratoglu SC. (2014). Low-density lipoprotein receptor-related protein-1: role in the regulation of vascular integrity. Arterioscler Thromb Vasc Biol 34:487–98 List EO, Berryman DE, Funk K, et al. (2014). Liver-specific GH receptor gene disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles. Endocrinology 155:1793–805 Coombs PJ, Taylor ME, Drickamer K. (2006). Two categories of mammalian galactose-binding receptors distinguished by glycan array profiling. Glycobiology 16:1C–7C Woods R, Greally J. (1979). Complement receptors on mouse foetal liver cells. Dev Comp Immunol 3:161–74 Deng X, Luyendyk JP, Ganey PE, Roth RA. (2009). Inflammatory stress and idiosyncratic hepatotoxicity: hints from animal models. Pharmacol Rev 61:262–82 Kedderis GL. (1996). Biochemical basis of hepatocellular injury. Toxicol Pathol 24:77–83 Bleibel W, Kim S, D’Silva K, Lemmer ER. (2007). Drug-induced liver injury: review article. Dig Dis Sci 52:2463–71 Chang C, Schiano T. (2007). Review article: drug hepatotoxicity. Aliment Pharmacol Ther 25:1135–51 Naruse K, Tang W, Makuuchi M. (2007). Artificial and bioartificial liver support: a review of perfusion treatment for hepatic failure patients. World J Gastroenterol 13:1516–21 Uetrecht J. (2005). Role of animal models in the study of drug-induced hypersensitivity reactions. AAPS J 7:E914–21 Olson H, Betton G, Robinson D, et al. (2000). Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 32:56–67 Murray KF, Hadzic N, Wirth S, et al. (2008). Drug-related hepatotoxicity and acute liver failure. J Pediatr Gastroenterol Nutr 47:395–405 Kaplowitz N. (2004). Drug-induced liver injury. Clin Infect Dis 38:S44–8 Saukkonen JJ, Cohn DL, Jasmer RM, et al. (2006). An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 174:935–52 Angulo P. (2002). Nonalcoholic fatty liver disease. N Engl J Med 346:1221–31 Langman G, Hall PDLM, Todd G. (2001). Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol 16:1395–401 Garg T, Singh O, Arora S, Murthy R. (2011). Patented microencapsulation techniques and its application. J Pharm Res 4:2097–102 King PD, Perry MC. (2001). Hepatotoxicity of chemotherapy. Semin Oncol 6:162–76 Ishak KG, Zimmerman HJ. (1995). Morphologic spectrum of drug-induced hepatic disease. Gastroenterol Clin North Am 24:759–86 Brind AM. (2007). Drugs that damage the liver. Medicine 35:26–30 Rollins BJ. (1986). Hepatic veno-occlusive disease. Am J Med 81:297–306 Kaplowitz N. (2001). Drug-induced liver disorders. Drug Saf 24:483–90 Arzt J, Mount M. (1999). Hepatotoxicity associated with pyrrolizidine alkaloid (Crotalaria spp) ingestion in a horse on Easter Island. Vet Hum Toxicol 41:96–9 Stickel F, Seitz H, Hahn E, Schuppan D. (2001). Liver toxicity of drugs of plant origin. Zeitsch Gastroenterol 39:225–32, 234–7 Stickel F, Egerer G, Seitz HK. (2000). Hepatotoxicity of botanicals. Public Health Nutr 3:113–24 Teschke R, Glass X, Schulze J, Eickhoff A. (2012). Suspected greater celandine hepatotoxicity: liver-specific causality evaluation of published case reports from Europe. Eur J Gastroenterol Hepatol 24:270–80 Haller CA, Dyer JE, Ko R, Olson KR. (2002). Evidence-based case reviews: making a diagnosis of herbal-related toxic hepatitis. West J Med 176:39–44 Kouzi SA, McMurtry RJ, Nelson SD. (1994). Hepatotoxicity of germander (Teucrium chamaedrys L.) and one of its constituent neoclerodane diterpenes teucrin A in the mouse. Chem Res Toxicol 7:850–6 Jeong SC, Kim SM, Jeong YT, Song CH. (2013). Hepatoprotective effect of water extract from Chrysanthemum indicum L. flower. Chin Med 8:7 Sharma OP, Makkar HPS, Dawra RK. (1988). A review of the noxious plant Lantana camara. Toxicon 26:975–87 Chan TY, Chan JC, Tomlinson B, Critchley JA. (1994). Poisoning by Chinese herbal medicines in Hong Kong: a hospital-based study. Vet Hum Toxicol 36:546–7 Henry SH, Bosch FX, Troxell TC, Bolger PM. (1999). Policy forum: public health. Reducing liver cancer – global control of aflatoxin. Science 286:2453–4 Daniele C, Dahamna S, Firuzi O, et al. (2005). Atractylis gummifera L. poisoning: an ethnopharmacological review. J Ethnopharmacol 97:175–81 Chitturi S, Farrell GC. (2002). Drug-induced liver disease. In: Schiff ER, Sorrell MF, Maddrey WC, eds. Schiff's diseases of the liver, 11th ed. Philadelphia: Lippincott-Raven, 703–83 Kao W-F, Hung D-Z, Tsai W-J, et al. (1992). Podophyllotoxin intoxication: toxic effect of Bajiaolian in herbal therapeutics. Hum Exp Toxicol 11:480–7 Larrey D. (1997). Hepatotoxicity of herbal remedies. J Hepatol 26:47–51 Gordon DW, Rosenthal G, Hart J, et al. (1995). Chaparral ingestionthe broadening spectrum of liver injury caused by herbal medications. JAMA 273:489–90 Om P. (2011). Clinical biochemistry of hepatotoxicity. J Clin Toxicol S4:1–19 Kälin P. (2003). The common butterbur (Petasites hybridus)–portrait of a medicinal herb. Forsch Komplementarmed Klass Naturheilkd 10:41–4. [In German] Yeong ML, Swinburn B, Kennedy M, Nicholson G. (1990). Hepatic veno-occlusive disease associated with comfrey ingestion. J Gastroenterol Hepatol 5:211–4 Wallace JL. (2004). Acetaminophen hepatotoxicity: NO to the rescue. Br J Pharmacol 143:1–2 Manokaran S, Jaswanth A, Sengottuvelu S, et al. (2008). Hepatoprotective activity of Aerva lanata Linn. against paracetamol induced hepatotoxicity in rats. Res J Pharm Technol 1:398–400 Navarro VJ, Senior JR. (2006). Drug-related hepatotoxicity. N Engl J Med 354:731–9 Arora N, Goldhaber SZ. (2006). Anticoagulants and transaminase elevation. Circulation 113:e698–702 Schimanski CC, Burg J, Möhler M, et al. (2004). Phenprocoumon-induced liver disease ranges from mild acute hepatitis to (sub-) acute liver failure. J Hepatol 41:67–74 Bhardwaj SS, Chalasani N. (2007). Lipid-lowering agents that cause drug-induced hepatotoxicity. Clin Liver Dis 11:597–613 Ricaurte B, Guirguis A, Taylor HC, Zabriskie D. (2006). Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity. Ann Pharmacother 40:753–7 Shimizu S, Atsumi R, Itokawa K, et al. (2009). Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice. Arch Toxicol 83:701–7 Moses G. (2005). Complementary and alternative medicine use in the elderly. J Pharm Pract Res 35:63–8 Piroth L. (2005). Liver steatosis in HIV-infected patients. AIDS Rev 7:197–209 Sulkowski MS, Mehta SH, Chaisson RE, et al. (2004). Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir. Aids 18:2277–84 Khalili H, Dashti-Khavidaki S, Rasoolinejad M, et al. (2009). Anti-tuberculosis drugs related hepatotoxicity; incidence, risk factors, pattern of changes in liver enzymes and outcome. Daru 17:163–7 Kremer JM, Lee RG, Tolman KG. (1989). Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. Arthritis Rheum 32:121–7 Edmondson HA, Peters RL. (1983). Tumors of the liver: pathologic features. Sem Roentgenol (Elsevier) 18:75–83 Iancu TC, Shiloh H, Dembo L. (1986). Hepatomegaly following short-term high-dose steroid therapy. J Pediatr Gastroenterol Nutr 5:41–6 O'Connor N, Dargan PI, Jones AL. (2003). Hepatocellular damage from non-steroidal anti-inflammatory drugs. QJM 96:787–91 Ezeuko Vitalis C, Nwokocha Chukwuemeka R, Mounmbegna Philippe E, et al. (2007). Effects of Zingiber officinale on liver function of mercuric chloride-induced hepatotoxicity in adult wistar rats. Electron J Biomed 3:40–5 Haleagrahara N, Jackie T, Chakravarthi S, et al. (2010). Protective effect of Etlingera elatior (torch ginger) extract on lead acetate-induced hepatotoxicity in rats. J Toxicol Sci 35:663–71 Pari L, Mohamed Jalaludeen A. (2011). Protective role of sinapic acid against arsenic-induced toxicity in rats. Chem Biol Interact 194:40–7 Boll M, Weber LW, Becker E, Stampfl A. (2001). Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by reactive carbon tetrachloride metabolites. Z Naturforsch C 56:649–59 Klaassen CD. (2001). Casarett and Doull's toxicology: the basic science of poisons. New York: McGraw-Hill Mochizuki M, Shimizu S, Urasoko Y, et al. (2009). Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats. J Toxicol Sci 34:175–81 Kuriakose GC, Kurup MG. (2011). Antioxidant and antihepatotoxic effect of Spirulina laxissima against carbon tetrachloride induced hepatotoxicity in rats. Food Funct 2:190–6 Purushotham KR, Lockard VG, Mehendale HM. (1988). Amplification of chloroform hepatotoxicity and lethality by dietary chlordecone (Kepone®) in mice. Toxicol Pathol 16:27–34 Jenkins L Jr, Trabulus M, Murphy S. (1972). Biochemical effects of 1,1-dichloroethylene in rats: comparison with carbon tetrachloride and 1,2-dichloroethylene. Toxicol Appl Pharmacol 23:501–10 Jaeger R, Trabulus M, Murphy S. (1973). Biochemical effects of 1, 1-dichloroethylene in rats: dissociation of its hepatotoxicity from a lipoperoxidative mechanism. Toxicol Appl Pharmacol 24:457–67 Shen D, Wu Q, Wang M, et al. (2006). Determination of the predominant catechins in Acacia catechu by liquid chromatography/electrospray ionization-mass spectrometry. J Agric Food Chem 54:3219–24 Raphael E. (2012). Phytochemical constituents of some leaves extract of Aloe vera and Azadirachta indica plant species. Global Adv Res J Environ Sci Toxicol 1:14–7 Mahesh A, Kumar H, Ranganath M, Devkar RA. (2012). Detail study on Boerhaavia diffusa plant for its medicinal importance – a review. Res J Pharm Sci 1:28–36 Colombo ML, Bosisio E. (1996). Pharmacological activities of Chelidonium majus L. (Papaveraceae). Pharmacol Res 33:127–34 Bishayee A, Sarkar A, Chatterjee M. (1995). Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver. J Ethnopharmacol 47:69–74 Singh G, Sharma P, Dudhe R, Singh S. (2010). Biological activities of Withania somnifera. Ann Biol Res 1:56–63 Verma VK, Siddiqui N. (2011). Bioactive chemical constituents from the plant Verbena officinalis Linn. Int J Pharm Pharm Sci 3:108–9 Khatri A, Garg A, Agrawal SS. (2009). Evaluation of hepatoprotective activity of aerial parts of Tephrosia purpurea L. and stem bark of Tecomella undulata. J Ethnopharmacol 122:1–5 Joseph B. (2011). Effect of bioactive compounds and its pharmaceutical activities of sida cordifolia (Linn.). Int J Biol Med Res 2:1038–42 Luper S. (1998). A review of plants used in the treatment of liver disease: part 1. Altern Med Rev J Clin Ther 3:410–21 Gagandeep Garg T, Malik B, Rath G, Goyal AK. (2014). Development and characterization of nano-fiber patch for the treatment of glaucoma. Eur J Pharm Sci 53:10–6 Singh V, Sharma S, Dhar K, Kalia A. (2013). Activity guided isolation of anti-inflammatory compound/fraction from root of Ricinus communis Linn. Int J PharmTech Res 5:1142–9 Lahon K, Das S. (2011). Hepatoprotective activity of Ocimum sanctum alcoholic leaf extract against paracetamol-induced liver damage in Albino rats. Pharmacognosy Res 3:13–8 Narendra K, Swathi J, Sowjanya K, Satya AK. (2012). Phyllanthus niruri: a review on its ethno botanical, phytochemical and pharmacological profile. J Pharm Res 5:4681–91 Perez-Amador M, Munoz Ocotero V, Ibarra Balcazar R, Garcia Jimenez F. (2010). Phytochemical and pharmacological studies on Mikania micrantha HBK (Asteraceae). Phyton Rev Int Bot Exp 79:77–80 Street RA, Sidana J, Prinsloo G. (2013). Cichorium intybus: traditional uses, phytochemistry, pharmacology, and toxicology. Evidence-Based Complement Altern Med 1–13 Nadim M, Malik AA, Ahmad J, Bakshi S. (2011). The essential oil composition of Achillea millefolium L. cultivated under tropical condition in India. World J Agric Sci 7:561–5 Shaikh M, Sancheti J, Sathaye S. (2012). Phytochemical and pharmacological investigations of Eclipta alba (Linn.) hassak leaves for antiepileptic activity. Int J Pharm Pharm Sci 4:77–80 Tabassum S, Mahmood S, Hanif J, et al. (2012). An overview of medicinal importance of SWERTIA CHIRAYITA. Int J Appl Sci Technol 2:298–304 Rawat A, Mehrotra S, Tripathi S, Shome U. (1997). Hepatoprotective activity of Boerhaavia diffusa L. roots – a popular Indian ethnomedicine. J Ethnopharmacol 56:61–6 Mortazavi SR, Nassiri-Asl M, Farahani-Nick Z, et al. (2007). Protective effects of Fumaria vaillantii extract on carbon tetrachloride induced hepatotoxicity in rats. Pharmacol Online 3:385–93 Lee C, Park S, Kim YS, et al. (2007). Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biol Pharm Bull 30:1898–904 Yamaura K, Shimada M, Nakayama N, Ueno K. (2011). Protective effects of goldenseal (Hydrastis canadensis L.) on acetaminophen-induced hepatotoxicity through inhibition of CYP2E1 in rats. Pharmacognosy Res 3:250–5 Cheng N, Ren N, Gao H, et al. (2013c). Antioxidant and hepatoprotective effects of Schisandra chinensis pollen extract on CCl4-induced acute liver damage in mice. Food Chem Toxicol 55:234–40 You Y, Yoo S, Yoon H-G, et al. (2010). In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress. Food Chem Toxicol 48:1632–7 Kim H-S, Lim H-K, Chung M-W, Kim YC. (2000). Antihepatotoxic activity of bergenin, the major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated hepatocytes. J Ethnopharmacol 69:79–83 Hattori Y, Nakamura A, Arai S, et al. (2014). In vivo siRNA delivery system for targeting to the liver by poly-l-glutamic acid-coated lipoplex. Results Pharma Sci 4:1–7 Garg T, Goyal AK. (2014b). Liposomes: targeted and controlled delivery system. Drug Deliv Lett 4:62–71 Bansal R, Prakash J, De Ruiter M, Poelstra K. (2014). Targeted recombinant fusion proteins of IFNγ and mimetic IFNγ with PDGFβR bicyclic peptide inhibits liver fibrogenesis in vivo. PLoS One 9:e89878 Sonoke S, Ueda T, Fujiwara K, et al. (2011). Galactose-modified cationic liposomes as a liver-targeting delivery system for small interfering RNA. Biol Pharm Bull 34:1338–42 Detampel P, Witzigmann D, Krähenbühl S, Huwyler J. (2013). Hepatocyte targeting using pegylated asialofetuin-conjugated liposomes. J Drug Target 22:1–10 Samy A, Elmowafy M, Arafa M, et al. (2014). Complement activation assay and in vivo evaluation of silymarin loaded liver targeting liposome. J Life Med 2 Elmowafy M, Viitala T, Ibrahim HM, et al. (2013). Silymarin loaded liposomes for hepatic targeting: in vitro evaluation and HepG2 drug uptake. Eur J Pharm Sci 50:161–71 Garg T, Goyal AK. (2012). Iontophoresis: drug delivery system by applying an electrical potential across the skin. Drug Deliv Lett 2:270–80 Tian J, Wang L, Wang L, Ke X. (2013). A wogonin-loaded glycyrrhetinic acid-modified liposome for hepatic targeting with anti-tumor effects. Drug Deliv 1–7 Narmada BC, Kang Y, Venkatraman L, et al. (2013). Hepatic stellate cell-targeted delivery of hepatocyte growth factor transgene via bile duct infusion enhances its expression at fibrotic foci to regress dimethylnitrosamine-induced liver fibrosis. Hum Gene Ther 24:508–19 Zhao C, Feng Q, Dou Z, et al. (2013). Local targeted therapy of liver metastasis from colon cancer by galactosylated liposome encapsulated with doxorubicin. PLoS One 8:e73860 Coulstock E, Sosabowski J, Ovečka M, et al. (2013). Liver-targeting of interferon-alpha with tissue-specific domain antibodies. PLoS one 8:e57263 Li C, Zhang D, Guo H, et al. (2013). Preparation and characterization of galactosylated bovine serum albumin nanoparticles for liver-targeted delivery of oridonin. Int J Pharm 448:79–86 Guo H, Zhang D, Li T, et al. (2014). In vitro and in vivo study of gal-os self-assembled nanoparticles for liver-targeting delivery of doxorubicin. J Pharm Sci 103:987–93 Mishra D, Jain N, Rajoriya V, Jain AK. (2014). Glycyrrhizin conjugated chitosan nanoparticles for hepatocyte-targeted delivery of lamivudine. J Pharm Pharmacol 66:1082–93 Cheng M, Gao X, Wang Y, et al. (2013a). Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo. Int J Nanomed 8:4265–76 Dangi R, Hurkat P, Jain A, et al. (2014). Targeting liver cancer via ASGP receptor using 5-FU-loaded surface-modified PLGA nanoparticles. J Microencapsul 31:1–9 Soni MP, Shelkar N, Gaikwad RV, et al. (2014). Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis. J Pharm Bioallied Sci 6:22–30 Jain D, Kumar A. (2013). Galactosylated poly(d,l-Lactic-co-glycolic acid) nanoparticles for liver targeted delivery of acyclovir. J Biomed Pharm Res 2:7–14 Cheng M, Xu H, Wang Y, et al. (2013b). Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells. Drug Des Dev Ther 7:1287–99 Ong ZY, Yang C, Gao SJ, et al. (2013). Galactose-functionalized cationic polycarbonate diblock copolymer for targeted gene delivery to hepatocytes. Macromol Rapid Commun 34:1714–20 Zhu XL, Du YZ, Yu RS, et al. (2013). Galactosylated chitosan oligosaccharide nanoparticles for hepatocellular carcinoma cell-targeted delivery of adenosine triphosphate. Int J Mol Sci 14:15755–66 Tian Q, Wang X-H, Wang W, et al. (2012). Self-assembly and liver targeting of sulfated chitosan nanoparticles functionalized with glycyrrhetinic acid. Nanomedicine Nanotechnol Biol Med 8:870–9 Huang W, Wang W, Wang P, et al. (2011). Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier. J Mater Sci Mater Med 22:853–63 Wang H-X, Xiong M-H, Wang Y-C, et al. (2013). N-acetylgalactosamine functionalized mixed micellar nanoparticles for targeted delivery of siRNA to liver. J Control Release 166:106–14 Li X, Huang Y, Chen X, et al. (2009). Self-assembly and characterization of Pluronic P105 micelles for liver-targeted delivery of silybin. J Drug Target 17:739–50 Wu D-Q, Lu B, Chang C, et al. (2009). Galactosylated fluorescent labeled micelles as a liver targeting drug carrier. Biomaterials 30:1363–71 Wu F, Xu T, Liu C, et al. (2013). Glycyrrhetinic acid-poly (ethylene glycol)-glycyrrhetinic acid tri-block conjugates based self-assembled micelles for hepatic targeted delivery of poorly water soluble drug. Sci World J 2013:1–10 Bei Y-Y, Yuan Z-Q, Zhang L, et al. (2014). Novel self-assembled micelles based on palmitoyl-trimethyl-chitosan for efficient delivery of harmine to liver cancer. Exp Opin Drug Deliv 11:843–54 Craparo EF, Sardo C, Serio R, et al. (2014). Galactosylated polymeric carriers for liver targeting of sorafenib. Int J Pharm 466:172–80 Zhu L, Mahato RI. (2010). Targeted delivery of siRNA to hepatocytes and hepatic stellate cells by bioconjugation. Bioconjug Chem 21:2119–27 Wang Y, Wang L, Liu Z, et al. (2012b). In vivo evaluation of silybin nanosuspensions targeting liver. J Biomed Nanotechnol 8:760–9 Wang L, Li M, Zhang N. (2012a). Folate-targeted docetaxel-lipid-based-nanosuspensions for active-targeted cancer therapy. Int J Nanomedicine 7:3281–94 Shegokar R, Singh KK. (2011). Surface modified nevirapine nanosuspensions for viral reservoir targeting: in vitro and in vivo evaluation. Int J Pharm 421:341–52 Vale N, Moreira R, Gomes P. (2009). Primaquine revisited six decades after its discovery. Eur J Med Chem 44:937–53 Jiwpanich S. (2011). Design and synthesis of a new class of self-cross-linked polymer nanogels. Dissertations, University of Massachusetts, Amherst Huang W, Wang W, Wang P, et al. (2010). Glycyrrhetinic acid-modified poly (ethylene glycol)–b-poly (γ-benzyl l-glutamate) micelles for liver targeting therapy. Acta Biomater 6:3927–35 Hashim F, El-Ridy M, Nasr M, Abdallah Y. (2010). Preparation and characterization of niosomes containing ribavirin for liver targeting. Drug Deliv 17:282–7 Jain S, Singh P, Mishra V, Vyas S. (2005). Mannosylated niosomes as adjuvant–carrier system for oral genetic immunization against Hepatitis B. Immunol Lett 101:41–9 Hong M, Zhu S, Jiang Y, et al. (2009). Efficient tumor targeting of hydroxycamptothecin loaded PEGylated niosomes modified with transferrin. J Control Release 133:96–102